The assessment of individual personal exposure to toxic substances is an important component of human and animal health risk assessment. Assessment of exposure by the analysis of breath is particularly attractive since it is noninvasive and nontraumatic for the subject. Breath may also be a less complex medium than blood or urine, and so may be easier to analyze and characterize. For these reasons, breath analysis has been applied in several studies addressing exposure to toxic chemicals, or investigating natural metabolites such as indicators of disease, see for example: A. Zlatkis, R. Brazell, and C. Poole, Clin. Chem., 27, 289-297, 1981; B. Krotoszyinski, G. Gabriel, and H. J. O'Neill, Chrom. Sci., 15, 239, 1977; S. Chen, L. Zieve, and V. Mahadevan, J. Lab. Clin. Med., 75, 628-635, 1970; M. Simenhoff, J. Burke, J. Saukkonen, A Ordinavio, and R. Doty, New England J. Med., 297, 132-135, 1977; B. Lorber, Amer. Rev. Resp. Dis., 112, 875-877, 1975; F. Brugnone, L. Perbellini, P. Apostoli, and E. Gaffuri, "Monitoring of Industrial Exposure to Organic Volatile Compounds by Analysis of Alveolar Air and Blood", American Chemical Society 187th National Meeting, St. Louis, Mo., 1985; M. Hisamura, Nippon Naika Gakkai Zasshi, 68, 1284-1292, 1979; A. Tangerman, M. T. Meuwese-Arends, J. H. M. van Tongeren, J. Lab Clin. Med., 106, 175-182, 1985; L. Campbell, D. M. Marsh, and H. K. Wilson, Ann Occup. Hyg., 31, 121-133, 1987; R. W. Handy, H. L. Crist, T. W. Stanley, "Quality Assurance For Personal Exposure Monitoring", in Quality Assurance For Environmental Measurements, ASTM Special Technical Publication No. 867, 284-296, 1985; and A. W. Jones, G. Maardh, E. Aenggard, Pharmoacol. Biochem. Behav., 18, 267-272, 1983. In most of the studies breath analysis has been performed by integrated collection of breath in bags, on sorbent materials, or in cryogenic traps. Such approaches may suffer from poor time resolution, inefficient sample collection or recovery, or sample degradation.
Further, breath analysis is useful in the study of natural metabolites, including indicators of disease, as well as bodily effects due to exposure to toxic chemicals. By monitoring whole breath continuously, in realtime, many studies in chemical toxicology, occupational medicine and exercise physiology can be performed.
Recently attempts have been made to apply the considerable sensitivity and selectivity of tandem mass spectrometry (MS/MS) to breath analysis, by employing atmospheric pressure chemical ionization (APCI) as the ionization source, see for example: A. M. Lovett, N. M. Reid, J. A. Buckley, J. B. French, and D. M. Cameron, Biomed. Mass Spectrom., 6, 91-97, 1979 F. M. Benoit, W. R. Davidson, A. M Lovett, S. Nacson, and A. Ngo, Anal. Chem., 55, 805-807, 1983; and F. M. Benoit, W. R. Davidson, A. M. Lovett, S. Nacson, and A. Ngo, Int. Arch. Occup. Environ. Health, 55, 113-120, 1985. However, such efforts have been limited by the means used to introduce breath into the mass spectrometer. The breath inlets used required the subject to control his breath flow rate or an observed pressure gauge reading during exhalation, required dilution of breath with a continuous flow of clean air, and provided only intermittent data (i.e., during each exhalation).
Other relevant art known to the inventors includes the following U.S. Pat. No.: 4,772,559 to Preti et al. discloses a method of detecting and diagnosing an individual to determine the presence of bronchiotic carcinoma by analysis of expired lung air; U.S. Pat. No. 4,485,822 to O'Connor et al. relates to a system and method for interfacing a patient with equipment for monitoring gaseous components of the exhalation of the patient and emphasizes the elimination of dead space volume and a disc filter for removing secretions and humidification; U.S. Pat. No. 4,178,919 to Hall reveals a flowmeter for providing synchronized flow data and respiratory gas samples to a medical mass spectrometer; U.S. Pat. No. 4,167,667 to Fletcher, et al. discloses a respiratory gas moisture separator system for mass spectrometer monitoring systems that relies on a pressure drop to maintain moisture in the vapor state and a momentum separator to remove water droplets; U.S. Pat. No. 3,759,249 to Fletcher, et al. relates to a method and apparatus for obtaining an analysis of respiratory gas flow rate and frequency of inspiration and expiration cycles on a "real time" basis; U.S. Pat. No. 3,649,199 to Littlejohn reveals a method for detecting trace quantities of an organic drug material in a living animal and relies on a membrane gas separator for direct breath analysis (column 3, lines 29-32); U.S. Pat. No. 3,622,278 to Etzinga discloses a method and means for measuring and analyzing the composition of alveolar air for determining the volatile constituents in blood. The device eliminates air from the dead air spaces of the respiratory tract thereby avoiding dilution of alveolar air.
An object of the present invention is to provide an improved breath interface which allows continuous analysis of undiluted breath by APCI/MS/MS. A further object is to provide an improved breath interface that reduces the loss of trace constituents in breath to a minimum. A still further object is to provide an improved breath interface that is easy to use and reliable.